title: Chronic alcohol alters dendritic spine development in neurons in primary culture.
abstract: Dendritic spines are specialised membrane protrusions of neuronal dendrites that receive the majority of excitatory synaptic inputs. Abnormal changes in their density, size and morphology have been associated with various neurological and psychiatric disorders, including those deriving from drug addiction. Dendritic spine formation, morphology and synaptic functions are governed by the actin cytoskeleton. Previous in vivo studies have shown that ethanol alters the number and morphology of spines, although the mechanisms underlying these alterations remain unknown. It has also been described how chronic ethanol exposure affects the levels, assembly and cellular organisation of the actin cytoskeleton in hippocampal neurons in primary culture. Therefore, we hypothesised that the ethanol-induced alterations in the number and shape of dendritic spines are due to alterations in the mechanisms regulating actin cytoskeleton integrity. The results presented herein show that chronic exposure to moderate levels of alcohol (30 mM) during the first 2 weeks of culture reduces dendritic spine density and alters the proportion of the different morphologies of these structures in hippocampal neurons, which affects the formation of mature spines. Apparently, these effects are associated with an increase in the G-actin/F-actin ratio due to a reduction of the F-actin fraction, leading to changes in the levels of the different factors regulating the organisation of this cytoskeletal component. The data presented herein indicate that these effects occur between weeks 1 and 2 of culture, an important period in dendritic spines development. These changes may be related to the dysfunction in the memory and learning processes present in children prenatally exposed to ethanol.
authors.affiliation: Sección de Biología y Patología Celular, Centro de Investigación, Hospital Universitario ''La Fe'', Avenida Campanar 21, 46009, Valencia, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Romero
authors.forename: Jaime
authors.initials: J
authors.lastname: Renau-Piqueras
authors.forename: M
authors.initials: M
authors.lastname: Pilar Marin
authors.forename: Joaquin
authors.initials: J
authors.lastname: Timoneda
authors.forename: Maria T
authors.initials: MT
authors.lastname: Berciano
authors.forename: Miguel
authors.initials: M
authors.lastname: Lafarga
authors.forename: Guillermo
authors.initials: G
authors.lastname: Esteban-Pretel
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D008841:Actin Cytoskeleton / Q000187:drug effects*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects* / Q000648:ultrastructure*; D000076122:Disks Large Homolog 4 Protein; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D058468:Receptors, Ionotropic Glutamate / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; C519154:IQGAP3 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D058468:Receptors, Ionotropic Glutamate; D020703:ras GTPase-Activating Proteins; D000431:Ethanol; D000110:Acetylcholinesterase